There currently is a worldwide epidemic of diabetes. Insulin resistance is recognized as a characteristic trait of the disease and is usually closely associated with obesity. Obesity also leads to a state of chronic, low-grade inflammation in liver and fat tissue, which in turn increases the levels of a pair of kinases: IKK-ε and TBK1. The asthma drug amlexanox is currently in clinical trials for the treatment of obesity and related metabolic disorders. Mechanistic studies in mice reveal that the compound improves the metabolism of sugar by generating a new signal between fat cells and the liver. Specifically, it exerts its effects by increasing the level of the second messenger molecule cAMP, which in turn increases the rate by which cells “burn” fat so that the animal loses weight. Amlexanox also triggers the release of the hormone interleukin-6 (IL-6) from fat cells, which then circulates to the liver. In the livers of diabetic mice, IL-6 reduces production of glucose, so that overall blood sugar is lowered. Amlexanox also improves nonalcoholic fatty liver disease (NAFLD) and NASH in mice and patients. However, clinically, amlexanox shows modest potency and non-optimal pharmacokinetics.